The present invention relates generally to medical treatments. More specifically, the present invention relates to solutions used for medical therapy including dialysis therapy, infusion therapy or the like.
Due to disease, insult or other causes, the renal system can fail. In renal failure of any cause, there are several physiological derangements. The balance of water, minerals (e.g., Na, K, Cl, Ca, P, Mg, SO4) and the excretion of a daily metabolic load of fixed ions is no longer possible in renal failure. During renal failure, toxic end products of nitrogen metabolism (e.g., urea, creatinine, uric acid, and the like) can accumulate in blood and tissues.
Dialysis processes have been devised for the separation of elements in a solution by diffusion across a semi-permeable membrane (diffusive solute transport) across a concentration gradient. Examples of dialysis processes include hemodialysis, peritoneal dialysis, hemofiltration and hemodiafiltration.
Hemodialysis treatment utilizes the patient's blood to remove waste, toxins, and excess water from the patient. The patient is connected to a hemodialysis machine and the patient's blood is pumped through the machine. Needles or catheters are inserted into the patient's veins and arteries to connect the blood flow to and from the hemodialysis machine. Waste, toxins, and excess water are removed from the patient's blood and the blood is infused back into the patient. Hemodialysis treatments can last several hours and are generally performed in a treatment center about three or four times per week.
To overcome the disadvantages often associated with classical hemodialysis, other techniques were developed, such as peritoneal dialysis, hemofiltration and hemodiafiltration. Peritoneal dialysis utilizes the patient's own peritoneum as a semipermeable membrane. The peritoneum is the membranous lining of the body cavity that, due to the large number of blood vessels and capillaries, is capable of acting as a natural semipermeable membrane.
In peritoneal dialysis, a sterile dialysis solution is introduced into the peritoneal cavity utilizing a catheter. After a sufficient period of time, an exchange of solutes between the dialysate and the blood is achieved. Fluid removal is achieved by providing a suitable osmotic gradient from the blood to the dialysate to permit water outflow from the blood. This allows a proper acid-base, electrolyte and fluid balance to be returned to the blood. The dialysis solution is simply drained from the body cavity through the catheter. Examples of different types of peritoneal dialysis include continuous ambulatory peritoneal dialysis, automated peritoneal dialysis and continuous flow peritoneal dialysis.
Hemofiltration is a convection-based blood cleansing technique. Blood access can be venovenous or arteriovenous. As blood flows through the hemofilter, a transmembrane pressure gradient between the blood compartment and the ultrafiltrate compartment causes plasma water to be filtered across the highly permeable membrane. As the water crosses the membrane, it convects small and large molecules across the membrane and thus cleanses the blood. An excessive amount of plasma water is eliminated by filtration. Therefore, in order to keep the body water balanced, fluid must be substituted continuously by a balanced electrolyte solution (replacement or substitution fluid) infused intravenously. This substitution fluid can be infused either into the arterial blood line leading to the hemofilter (predilution) or into the venous blood line leaving the hemofilter (post dilution).
In addition to the removal of metabolic products, one of the most important problems of every kidney replacement therapy, such as hemodialysis, hemofiltration and peritoneal dialysis, lies in the correction of metabolic acidosis. For this reason, the dialysis solutions used in each of these processes contain a buffer.
Three common buffers often used in dialysis solutions are bicarbonate, lactate and acetate. While initially bicarbonate was the primary buffer used in dialysis solutions, over time lactate and acetate were used as substitutes for bicarbonate. This was due to the difficulty in preparation and storage of bicarbonate-buffered dialysis solutions. Lactate and acetate buffers are known to provide greater stability in use over the previous bicarbonate-buffered solutions.
However, since bicarbonate ions provide advantages over acetate or lactate ions, bicarbonate is again surfacing as the primary buffer used in dialysis solutions. Tests have been conducted that indicate patients exhibit a better tolerance for bicarbonate dialysis solutions. In patients with a multiple organ failure, bicarbonate-buffered solutions are preferred because of the lack of metabolic interference. Further, certain treatments require sterile dialysis solutions containing bicarbonate, calcium and magnesium.
But, in the presence of bicarbonate, these ions can form calcium carbonate and magnesium carbonate, respectively, which at increased pHs typically precipitate from the solution. To initially remedy this problem, bicarbonate solutions are often made from concentrates, ranging from slightly concentrated, two-fold or less, to much more concentrated solutions. Further, the bicarbonate on the one hand and calcium and/or magnesium on the other hand are included in separate concentrates and stored separately prior to use. For example, the concentrates can be stored in separate containers or separate chambers of a multi-chamber container. The bicarbonate concentrate and the concentrate of electrolytes that can include calcium, magnesium and the like are then mixed just prior to use to prevent the precipitation of carbonates.
However, the use of a multi-chamber container or individual containers to separately store the bicarbonate concentrate and the electrolyte concentrate prior to use can increase the amount of time and effort that is needed to perform dialysis therapy. With the use of a bicarbonate-based solution in a multi-chamber container, the patient is typically required to break a frangible to allow the concentrates to mix prior to use. Further, if a gas barrier overpouch is used with the multi-chamber container, the overpouch is typically removed prior to mixing. If the gas barrier overpouch is not removed, the breaking of the frangible can damage the gas barrier, thus causing a loss of long term solution stability.
Further, the use of a multiple number of individual containers to separately store the concentrates prior to mixing can require additional handling and storage capacity. U.S. Pat. No. 5,296,242 (“Zander”) describes the use of a stable aqueous solution in the form of two separately stored single solutions, one containing a metabolizable organic acid, and the other alkali bicarbonate and alkali carbonate. The Zander patent relates to adjusting the pH of the dextrose compartment with an organic acid; the dextrose compartment is adjusted to a pH range of 4.0 to 6.0. Not only do the inventors believe a physiological solution will not be achieved with such a high pH for the dextrose component, problems arise from the use of organic acids. For example, in patients with liver failure the body has difficulty in metabolizing organic acids, and it is therefore preferable to have all buffer available as bicarbonate. In case of peritoneal dialysis, the presence of organic acids and dextrose in the same container will enhance the formation of glucose degradation products, which in turn may damage the peritoneal membrane.
Bicarbonate-based solutions are known which require the use of a stabilizing agent in addition to bicarbonate and other constituents, such as calcium and magnesium. For example, U.S. Pat. No. 4,959,175 discloses the use of stabilizing agents, such as glycylglycine, to prevent the precipitation of carbonates. European Patent Document No. EP 1166787 discloses the use of other types of stabilization agents, such as disodium hydrogen citrate. However, the use of stabilizing agents may have undesirable side effects.
Therefore, a need exists to provide improved bicarbonate-based solutions that can be readily manufactured, that can remain stable and sterile under storage conditions, and that can be readily and effectively used during medical therapy, such as dialysis therapy.